Lung Infection

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Niels Høiby - One of the best experts on this subject based on the ideXlab platform.

  • quorum sensing and virulence of pseudomonas aeruginosa during Lung Infection of cystic fibrosis patients
    PLOS ONE, 2010
    Co-Authors: Thomas Bjarnsholt, Michael Givskov, Niels Høiby, Peter Ostrup Jensen, Tim Holm Jakobsen, Richard Kerry Phipps, Anne K Nielsen, Morten Rybtke, Tim Tolkernielsen, Oana Ciofu
    Abstract:

    Pseudomonas aeruginosa is the predominant microorganism in chronic Lung Infection of cystic fibrosis patients. The chronic Lung Infection is preceded by intermittent colonization. When the chronic Infection becomes established, it is well accepted that the isolated strains differ phenotypically from the intermittent strains. Dominating changes are the switch to mucoidity (alginate overproduction) and loss of epigenetic regulation of virulence such as the Quorum Sensing (QS). To elucidate the dynamics of P. aeruginosa QS systems during long term Infection of the CF Lung, we have investigated 238 isolates obtained from 152 CF patients at different stages of Infection ranging from intermittent to late chronic. Isolates were characterized with regard to QS signal molecules, alginate, rhamnolipid and elastase production and mutant frequency. The genetic basis for change in QS regulation were investigated and identified by sequence analysis of lasR, rhlR, lasI and rhlI. The first QS system to be lost was the one encoded by las system 12 years (median value) after the onset of the Lung Infection with subsequent loss of the rhl encoded system after 17 years (median value) shown as deficiencies in production of the 3-oxo-C12-HSL and C4-HSL QS signal molecules respectively. The concomitant development of QS malfunction significantly correlated with the reduced production of rhamnolipids and elastase and with the occurrence of mutations in the regulatory genes lasR and rhlR. Accumulation of mutations in both lasR and rhlR correlated with development of hypermutability. Interestingly, a higher number of mucoid isolates were found to produce C4-HSL signal molecules and rhamnolipids compared to the non-mucoid isolates. As seen from the present data, we can conclude that P. aeruginosa and particularly the mucoid strains do not lose the QS regulation or the ability to produce rhamnolipids until the late stage of the chronic Infection.

  • Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa Lung Infection in mice.
    Journal of Antimicrobial Chemotherapy, 2004
    Co-Authors: Zhijun Song, Morten Hentzer, Jens Bo Andersen, Søren Molin, Michael Givskov, Niels Høiby
    Abstract:

    Introduction: Antibiotics are used to treat bacterial Infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways to control certain bacterial Infections. Furanone compounds capable of inhibiting bacterial quorum-sensing systems have been isolated from the marine macro alga Delisea pulchra. Objectives: Two synthetic furanones were tested for their ability to attenuate bacterial virulence in the mouse models of chronic Lung Infection by targeting bacterial quorum-sensing without directly killing bacteria or inhibiting their growth. Methods: Study I. Mice with Escherichia coli MT102 [luxR-Pluxl-gfp(ASV)] Lung Infection were injected intravenously with N-acyl homoserine lactones with or without furanones to test the interference of furanones with quorum-sensing. Study II. Mice with Lung Infection by Pseudomonas aeruginosa PAO1 [dsred, lasR-PlasB-gfp(ASV)] were injected intravenously with furanones to evaluate their inhibiting effects on quorum-sensing. Study III. Mice with P. aeruginosa PAO1 Lung Infection were treated with different doses of furanones to evaluate the therapeutic effects of furanones on the Lung Infection. Results: Furanones successfully interfered with N-acyl homoserine lactone and suppressed bacterial quorum-sensing in Lungs, which resulted in decreases in expression of green fluorescent protein. Furanones accelerated Lung bacterial clearance, and reduced the severity of Lung pathology. In a lethal P. aeruginosa Lung Infection, treatment with furanone significantly prolonged the survival time of the mice. Conclusion: Synthetic furanone compounds inhibited bacterial quorum-sensing in P. aeruginosa and exhibited favourable therapeutic effects on P. aeruginosa Lung Infection.

Zhang Yinqin - One of the best experts on this subject based on the ideXlab platform.

  • Clinical Study of Mucosolvan in Treatment of Lung Infection after Severe Brain Injury
    The Journal of Medical Theory and Practice, 2003
    Co-Authors: Zhang Yinqin
    Abstract:

    Objective: To study the therapeutic effect of Mucosolvan on Lung Infection after severe brain injury. Methods: All 90 patients with Lung cancer after severe brain injury (Glasgow coma scale score of 8 or less on admission) were randomly divided into the experimental group(45 cases) and the control group(45 cases) .The experimental group were treated by Mucosolvan and the control group treated without Mucosolvan. Results: The results showed that 42 cases of Lung Infection were controlled in the experimental group while in the control group,35 cases were controlled respectively.There were significant difference in two groups (P 0.05); The time of Lung Infection controlled in the experimental group were shorter than that in control group (P 0.01) . Conclusions:The effect of patients with Lung Infection after severe brain injury can be improved by administration Mucosolvan and it deserves further clinical applications.

Michael Givskov - One of the best experts on this subject based on the ideXlab platform.

  • quorum sensing and virulence of pseudomonas aeruginosa during Lung Infection of cystic fibrosis patients
    PLOS ONE, 2010
    Co-Authors: Thomas Bjarnsholt, Michael Givskov, Niels Høiby, Peter Ostrup Jensen, Tim Holm Jakobsen, Richard Kerry Phipps, Anne K Nielsen, Morten Rybtke, Tim Tolkernielsen, Oana Ciofu
    Abstract:

    Pseudomonas aeruginosa is the predominant microorganism in chronic Lung Infection of cystic fibrosis patients. The chronic Lung Infection is preceded by intermittent colonization. When the chronic Infection becomes established, it is well accepted that the isolated strains differ phenotypically from the intermittent strains. Dominating changes are the switch to mucoidity (alginate overproduction) and loss of epigenetic regulation of virulence such as the Quorum Sensing (QS). To elucidate the dynamics of P. aeruginosa QS systems during long term Infection of the CF Lung, we have investigated 238 isolates obtained from 152 CF patients at different stages of Infection ranging from intermittent to late chronic. Isolates were characterized with regard to QS signal molecules, alginate, rhamnolipid and elastase production and mutant frequency. The genetic basis for change in QS regulation were investigated and identified by sequence analysis of lasR, rhlR, lasI and rhlI. The first QS system to be lost was the one encoded by las system 12 years (median value) after the onset of the Lung Infection with subsequent loss of the rhl encoded system after 17 years (median value) shown as deficiencies in production of the 3-oxo-C12-HSL and C4-HSL QS signal molecules respectively. The concomitant development of QS malfunction significantly correlated with the reduced production of rhamnolipids and elastase and with the occurrence of mutations in the regulatory genes lasR and rhlR. Accumulation of mutations in both lasR and rhlR correlated with development of hypermutability. Interestingly, a higher number of mucoid isolates were found to produce C4-HSL signal molecules and rhamnolipids compared to the non-mucoid isolates. As seen from the present data, we can conclude that P. aeruginosa and particularly the mucoid strains do not lose the QS regulation or the ability to produce rhamnolipids until the late stage of the chronic Infection.

  • Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa Lung Infection in mice.
    Journal of Antimicrobial Chemotherapy, 2004
    Co-Authors: Zhijun Song, Morten Hentzer, Jens Bo Andersen, Søren Molin, Michael Givskov, Niels Høiby
    Abstract:

    Introduction: Antibiotics are used to treat bacterial Infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways to control certain bacterial Infections. Furanone compounds capable of inhibiting bacterial quorum-sensing systems have been isolated from the marine macro alga Delisea pulchra. Objectives: Two synthetic furanones were tested for their ability to attenuate bacterial virulence in the mouse models of chronic Lung Infection by targeting bacterial quorum-sensing without directly killing bacteria or inhibiting their growth. Methods: Study I. Mice with Escherichia coli MT102 [luxR-Pluxl-gfp(ASV)] Lung Infection were injected intravenously with N-acyl homoserine lactones with or without furanones to test the interference of furanones with quorum-sensing. Study II. Mice with Lung Infection by Pseudomonas aeruginosa PAO1 [dsred, lasR-PlasB-gfp(ASV)] were injected intravenously with furanones to evaluate their inhibiting effects on quorum-sensing. Study III. Mice with P. aeruginosa PAO1 Lung Infection were treated with different doses of furanones to evaluate the therapeutic effects of furanones on the Lung Infection. Results: Furanones successfully interfered with N-acyl homoserine lactone and suppressed bacterial quorum-sensing in Lungs, which resulted in decreases in expression of green fluorescent protein. Furanones accelerated Lung bacterial clearance, and reduced the severity of Lung pathology. In a lethal P. aeruginosa Lung Infection, treatment with furanone significantly prolonged the survival time of the mice. Conclusion: Synthetic furanone compounds inhibited bacterial quorum-sensing in P. aeruginosa and exhibited favourable therapeutic effects on P. aeruginosa Lung Infection.

Joan Mecsas - One of the best experts on this subject based on the ideXlab platform.

  • yersinia pseudotuberculosis uses ail and yada to circumvent neutrophils by directing yop translocation during Lung Infection
    Cellular Microbiology, 2014
    Co-Authors: Michelle K Paczosa, Michael L Fisher, Francisco J Maldonadoarocho, Joan Mecsas
    Abstract:

    Summary A Yersinia pseudotuberculosis (Yptb) murine model of Lung Infection was previously developed using the serotype III IP2666NdeI strain, which robustly colonized Lungs but only sporadically dis- seminated to the spleen and liver. We demonstrate here that a serotype Ib Yptb strain, IP32953, colo- nizes the Lungs at higher levels and disseminates more efficiently to the spleen and liver compared with IP2666NdeI. The role of adhesins was investi- gated during IP32953 Lung Infection by construct- ing isogenic Δail, Δinv, ΔpsaE and ΔyadA mutants. An IP32953ΔailΔyadA mutant initially colonized but failed to persist in the Lungs and disseminate to the spleen and liver. Yptb expressing these adhesins selectively bound to and targeted neutrophils for translocation of Yops. This selective targeting was critical for virulence because persistence of the ΔailΔyadA mutant was restored following intrana- sal Infection of neutropenic mice. Furthermore, Ail and YadA prevented killing by complement- mediated mechanisms during dissemination to and/or growth in the spleen and liver, but not in the Lungs. Combined, these results demonstrate that Ail and YadA are critical, redundant virulence factors during Lung Infection, because they thwart neutrophils by directing Yop-translocation specifi- cally into these cells.

  • intranasal inoculation of mice with yersinia pseudotuberculosis causes a lethal Lung Infection that is dependent on yersinia outer proteins and phop
    Infection and Immunity, 2007
    Co-Authors: Michael L Fisher, Cynthia Castillo, Joan Mecsas
    Abstract:

    Yersinia pseudotuberculosis infects many mammals and birds including humans, livestock, and wild rodents and can be recovered from the Lungs of infected animals. To determine the Y. pseudotuberculosis factors important for growth during Lung Infection, we developed an intranasal model of Infection in mice. Following intranasal inoculation, we monitored both bacterial growth in Lungs and dissemination to systemic tissues. Intranasal inoculation with as few as 18 CFU of Y. pseudotuberculosis caused a lethal Lung Infection in some mice. Over the course of 7 days, wild-type Y. pseudotuberculosis replicated to nearly 1 × 108 CFU/g of Lung in BALB/c mice, induced histopathology in Lungs consistent with pneumonia, but disseminated sporadically to other tissues. In contrast, a ΔyopB deletion strain was attenuated in this model, indicating that translocation of Yersinia outer proteins (Yops) is essential for virulence. Additionally, a ΔyopH null mutant failed to grow to wild-type levels by 4 days postintranasal inoculation, but deletions of any other single effector YOP did not attenuate Lung colonization 4 days postInfection. Strains with deletions in yopH and any one of the other known effector yop genes were more attenuated that the ΔyopH strain, indicating a unique role for yopH in Lungs. In summary, we have characterized the progression of a Lung Infection with an enteric Yersinia pathogen and shown that YopB and YopH are important in Lung colonization and dissemination. Furthermore, this Lung Infection model with Y. pseudotuberculosis can be used to test potential therapeutics against Yersinia and other gram-negative Infections in Lungs.

Haichen Sun - One of the best experts on this subject based on the ideXlab platform.

  • therapeutic effect of gastrotomy on Lung Infection and dystrophy in patients with traumatic vagus nerve injury
    Chinese Journal of Trauma, 2015
    Co-Authors: Chao Lin, Qiyong Mei, Kaiwei Han, Hai Jin, Shun Gong, Ning Liu, Haichen Sun
    Abstract:

    Objective To examine the occurrence of traumatic lower cranial nerve injury and the therapeutic effect of gastrostomy on vagus nerve injury. Methods Clinical data of 45 patients sustaining traumatic lower cranial nerve injury were retrospectively analyzed. There were 32 males and 13 females, with the age of (34.5±8.8)years. Injury resulted from high falls in 22 patients, traffic accidents in 15 patients and other in 8 patients. Non-operative treatments, nutrition and hormone intervention, improving minicirculation, promoting blood circulation and removing stasis for instance, were performed for the patients with the injury involving the glossopharyngeal nerve (n=12), accessory nerve (n=21) and hypoglossal nerve (n=20). Vagus nerve injury was seen in 32 patients. Fifteen out of the 32 patients underwent gastrotomy and early enteral nutrition support and 17 transnasal gastric catheter indwelling and enteral nutrition support. Lung Infection and dystrophy were evaluated after operation. Results Two patients had Lung Infection and one dystrophy after gastrotomy. In contrast, 9 patients had Lung Infection and one dystrophy after transnasal stomach intubation surgery (P<0.05). At follow-up, the complications were cured in gastrotomy group, but only 7 Lung Infection and 5 dystrophy were cured in indwelling catheter group. Conclusions Vagus nerve injury is most common in lower cranial nerve injury and manifested with choking on water and dysphagia. Gastrostomy in combination with early enteral nutrition therapy is effective to improve the nutritional status and reduce Lung Infection in patients with traumatic vagus nerve injury. Key words: Cranial nerve injuries; Traumatic brain injuries; Vagus nerve; Gastrostomy

  • Therapeutic effect of gastrotomy on Lung Infection and dystrophy in patients with traumatic vagus nerve injury
    Chinese Journal of Trauma, 2015
    Co-Authors: Chao Lin, Qiyong Mei, Kaiwei Han, Shun Gong, Ning Liu, Jin Hai, Gu Jinmao, Haichen Sun
    Abstract:

    Objective To examine the occurrence of traumatic lower cranial nerve injury and the therapeutic effect of gastrostomy on vagus nerve injury. Methods Clinical data of 45 patients sustaining traumatic lower cranial nerve injury were retrospectively analyzed. There were 32 males and 13 females, with the age of (34.5±8.8)years. Injury resulted from high falls in 22 patients, traffic accidents in 15 patients and other in 8 patients. Non-operative treatments, nutrition and hormone intervention, improving minicirculation, promoting blood circulation and removing stasis for instance, were performed for the patients with the injury involving the glossopharyngeal nerve (n=12), accessory nerve (n=21) and hypoglossal nerve (n=20). Vagus nerve injury was seen in 32 patients. Fifteen out of the 32 patients underwent gastrotomy and early enteral nutrition support and 17 transnasal gastric catheter indwelling and enteral nutrition support. Lung Infection and dystrophy were evaluated after operation. Results Two patients had Lung Infection and one dystrophy after gastrotomy. In contrast, 9 patients had Lung Infection and one dystrophy after transnasal stomach intubation surgery (P